Design, synthesis and the evaluation of cholinesterase inhibition and blood‐brain permeability of daidzein derivatives or analogs.

In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood–brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7‐hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'‐N,N‐dimethylaminoethoxy‐7‐methoxyisoflavone) appeared the best inhibitory activity (IC50: 2.14 ± 0.31 μmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC‐MS/MS. The results show that CBrain/Serum of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]